Effect of 5-HT5A antagonists in animal models of schizophrenia, anxiety and depression.

Abstract

The few available data on the pharmacological effect of 5-HT5A receptors suggest that antagonists may have anxiolytic, antidepressant and antipsychotic activity. The aim of our study was to verify these suggestions in relevant animal models. Two 5-HT5A antagonist ligands, SB-699551-A (N-[2-(dimethylamino)ethyl]-N-[[4'-[[(2-phenylethyl)amino]methyl][1,1'-biphenyl]-4-yl]methyl]cyclopentanepropanamide dihydrochloride) (3-60 mg/kg, intraperitoneally) and A-843277 (N-(2,6-dimethoxybenzyl)-N'[4-(4-fluorophenyl)thiazol-2-yl]guanidine) (3-30 mg/kg, intraperitoneally), were examined in the open-field test, in a foot-shock-induced ultrasonic vocalization test, in the forced swim test (FST) and in the amphetamine-induced and phencyclidine-induced hyperlocomotion tests to examine their effect on general behavioural patterns, and their anxiolytic-like, antidepressant-like and antipsychotic-like properties, respectively. In the open-field test, SB-699551-A induced sedation and A-843277 induced writhing. In the ultrasonic vocalization test, SB-699551-A reduced vocalizations, whereas A-843277 was ineffective. In the FST, SB-699551-A was ineffective and A-843277 reduced immobility, but only at the highest dose. In the amphetamine-induced and phencyclidine-induced hyperlocomotion test, both compounds were ineffective. SB-699551-A showed an anxiolytic-like property in the ultrasonic vocalization test; however, this compound has a sedative effect. A-843277 showed an antidepressant-like property in the FST, but its immobility-reducing effect may also be a consequence of abdominal irritation. Consequently, further investigations are required to define the therapeutic potential of 5-HT5A receptor ligands in anxiety, depression and schizophrenia models.

• Authors: Ferenc Kassai, Chantal Schlumberger, Rita Kedves, Malgorzata Pietraszek, Claudia Jatzke, Balázs Lendvai, István Gyertyán, Wojciech Danysz
• Journal: Behavioural pharmacology (Behav Pharmacol) Vol. 23 Issue 4 Pg. 397-406 (Aug 2012) ISSN: 1473-5849 [Electronic] England
• PMID: 22785385 (Publication Type: Journal Article)

Chemical References

• Anti-Anxiety Agents
• Antidepressive Agents
• Antipsychotic Agents
• Biphenyl Compounds
• Guanidines
• N-(2,6-dimethoxybenzyl)-N'-(4-(4-fluorophenyl)thiazol-2-yl)guanidine
• Receptors, Serotonin
• SB-699551-A
• Serotonin Antagonists
• Thiazoles
• serotonin 5 receptor

Topics

• Animals
• Anti-Anxiety Agents (administration & dosage, pharmacology)
• Antidepressive Agents (administration & dosage, pharmacology)
• Antipsychotic Agents (administration & dosage, pharmacology)
• Anxiety (drug therapy, physiopathology)
• Biphenyl Compounds (administration & dosage, pharmacology)
• Depression (drug therapy, physiopathology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Guanidines (administration & dosage, pharmacology)
• Male
• Rats
• Rats, Wistar
• Receptors, Serotonin (drug effects, metabolism)
• Schizophrenia (drug therapy, physiopathology)
• Serotonin Antagonists (administration & dosage, pharmacology)
• Swimming
• Thiazoles (administration & dosage, pharmacology)
• Vocalization, Animal (drug effects)